BMP-7诱导NOTCH信号活化对氧糖剥夺Wistar胎鼠海马神经元保护的作用  

The protection effect of BMP-7 on cultured hippocampal neurons in oxygen-glucose deprivation/reperfusion Wistar rat via activation NOTCH signal

作　　者：关俊宏[1] 衣博龙 曲圣涛[1] 吕涛[1] 付强[1] 袁野[1] GUAN Jun-hong YI Bo-long QU Sheng-tao LV Tao FU Qiang YUAN Ye(Department of Neurosurgery, Shengjing Hospital of China Medical University, Liaoning Shenyang 110004, China)

机构地区：[1]中国医科大学附属盛京医院神经外科,辽宁沈阳110004

出　　处：《解剖科学进展》2017年第3期312-316,共5页Progress of Anatomical Sciences

基　　金：辽宁省自然科学基金(2015020504)

摘　　要：目的探讨骨形态发生蛋白-7(Bone morphogenetic protein-7,BMP-7)对氧糖剥夺处理海马神经元的保护作用及其机制。方法实验应用Wistar胎鼠,分为常规培养组(Control)、氧糖剥夺组(oxygen-glucose deprivation/reperfusion group,OGD/R)及2.5、5、10μM BMP-7干预处理组,并设置Notch信号抑制剂DAPT干预组。海马神经元细胞体外氧糖剥夺2 h后再灌注至24 h建立损伤模型;MTT法和乳酸盐脱氢酶(lactate dehydrogenase,LDH)释放实验检测细胞活化和凋亡情况,Western blot法检测Notch信号相关分子Notch-1、Notch-2、Jag-1、Hes1及凋亡相关蛋白Bcl-2、Bax、cleaved-caspase3的表达。结果BMP-7处理上调细胞活力并减少LDH释放,并上调Notch-1、Notch-2、Jag-1、Hes1的表达水平。DAPT干预处理后,BMP-7作用被抑制,细胞活力下降,LDH释放增多,抗凋亡蛋白Bcl-2表达水平降低,凋亡蛋白Bax、cleaved-caspase3表达水平升高。结论BMP-7对氧糖剥夺海马神经元的保护作用可能与活化Notch信号相关。Objective To study the protection effect and possible mechanism of BMP-7 on hippocampal neurons cultured in oxygen-glucose deprivation/reperfusion Wistar rats. Methods The experiments were divided into routine culture group （Control）, OGD/R （oxygen-glucose deprivation/reperfusion） group and 2.5, 5, 10 μM BMP-7 intervention group, and the Notch signal inhibitor DAPT was used to interven the effect of BMP-7. The hippocampal neurons were cultured in oxygen-glucose deprivation for 2 hours, then reperfusion for 24 hours to establish injury model in vitro. MTT assay and LDH（lactate dehydrogenase） release assay were used to test cell activation and apoptosis, the expression of Notch signal related molecules （Notch-l,Notch-2,Jag-1 and Hesl） and apoptosis related proteins（ Bcl-2, Bax and cleaved-caspase3） were detected by Western blotting. Results BMP-7 improved the cell viability and reduced LDH release, upregulated Notch-l, Notch-2, Jag-1 and Hesl expression levels significantly. After intervention with DAPT, the protective effect of BMP-7 on the cell viability was inhibited, the release of LDH was increased, the expression levels of Bax and cleaved- caspase 3 were increased, and the expression level of anti-apoptotic protein Bcl-2 was decreased. Conclusion The protective effect of BMP-7 on hippocampal neurons cultured in oxygen-glucose deprivation/reperfusion might be related to the activation of Notch signal.

关 键 词：氧糖剥夺 海马神经元 骨形态发生蛋白-7 NOTCH信号 Wistar胎鼠 

分 类 号：R743.31[医药卫生—神经病学与精神病学]